The major purpose of this project is to dissect the mechanism by which immunoglobulin and T-cell receptor genes are assembled into functional entities, and to study the regulation of this reaction. Several new results on this process, generally called V(D)J recombination, have been obtained. (1) Recombinants formed in fibroblast cell lines which express the RAG- 1 and RAG-2 genes rarely contain the added nucleotides which are characteristic of recombinants from lymphoid cells. The probable explanation is that fibroblasts lack the enzyme terminal deoxynucleotidyl transferase. (2) The recombinational defect of cell lines derived from mice with the scid mutation can be partly overcome by altering the cell culture conditions. The mutation is therefore leaky. (3) A molecular explanation for the preference of deletional over inversional D to J recombination at the immunoglobulin heavy-chain locus has emerged. The difference is due to several individually minor mutations in the upstream signal sequence associated with D regions.